Caspase 2
Encyclopedia
Caspase 2 also known as CASP2 is an enzyme
that, in humans, is encoded by the CASP2 gene
. CASP2 orthologs have been identified in nearly all mammals for which complete genome data are available. Unique orthologs are also present in birds, lizards, lissamphibians, and teleosts.
s plays a central role in the execution-phase of cell apoptosis
. Caspases exist as inactive proenzymes that undergo proteolytic processing at conserved aspartic
residues to produce two subunits, large and small, that dimerize to form the active enzyme. The proteolytic cleavage of this protein is induced by a variety of apoptotic stimuli.
Caspase 2 proteolytically
cleaves other proteins. It belongs to a family of cysteine protease
s called caspase
s that cleave proteins only at an amino acid
following a aspartic acid
residue. Within this family, caspase 2 is part of the Ich-1 subfamily. It is one of the most conserved caspases in different species
of animal. Caspase 2 has a similar amino acid sequence to initiator caspases, including caspase 1
, caspase 4
, caspase 5
, and caspase 9. It is produced as a zymogen
, which contains a long pro-domain that is similar to that of caspase 9 and contains a protein interaction domain known as a CARD domain
. Pro-caspase-2 contains two subunits, p19 and p12.
It has been shown to associate with several proteins involved in apoptosis
using its CARD domain, including RIP-associated Ich-1/Ced-3-homologue protein with a death domain (RAIDD), apoptosis repressor with caspase recruitment domain (ARC), and death effector filament-forming Ced-4-like apoptosis protein (DEFCAP). Together with RAIDD and p53-induced protein with a death domain ([PIDD])(LRDD
), caspase 2 has been shown to form the so called PIDDosome, which may serve as an activation platform for the protease, although it may also be activated in the absence of PIDD. In addition, caspase 2 may form a complex with the catalytic subunit of DNA-PK (DNA-PKcs) and PIDD (LRDD
), which is involved in DNA repair after DNA damage. Overall, caspase 2 appears to be a very versatile caspase with multiple functions beyond cell death induction.
with CRADD
, Caspase 8
and BH3 interacting domain death agonist
.
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
that, in humans, is encoded by the CASP2 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. CASP2 orthologs have been identified in nearly all mammals for which complete genome data are available. Unique orthologs are also present in birds, lizards, lissamphibians, and teleosts.
Function
Sequential activation of caspaseCaspase
Caspases, or cysteine-aspartic proteases or cysteine-dependent aspartate-directed proteases are a family of cysteine proteases that play essential roles in apoptosis , necrosis, and inflammation....
s plays a central role in the execution-phase of cell apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
. Caspases exist as inactive proenzymes that undergo proteolytic processing at conserved aspartic
Aspartic acid
Aspartic acid is an α-amino acid with the chemical formula HOOCCHCH2COOH. The carboxylate anion, salt, or ester of aspartic acid is known as aspartate. The L-isomer of aspartate is one of the 20 proteinogenic amino acids, i.e., the building blocks of proteins...
residues to produce two subunits, large and small, that dimerize to form the active enzyme. The proteolytic cleavage of this protein is induced by a variety of apoptotic stimuli.
Caspase 2 proteolytically
Proteolysis
Proteolysis is the directed degradation of proteins by cellular enzymes called proteases or by intramolecular digestion.-Purposes:Proteolysis is used by the cell for several purposes...
cleaves other proteins. It belongs to a family of cysteine protease
Cysteine protease
Proteases are enzymes that degrade polypeptides. Cysteine proteases have a common catalytic mechanism that involves a nucleophilic cysteine thiol in a catalytic dyad. The first step is deprotonation of a thiol in the enzyme's active site by an adjacent amino acid with a basic side chain, usually a...
s called caspase
Caspase
Caspases, or cysteine-aspartic proteases or cysteine-dependent aspartate-directed proteases are a family of cysteine proteases that play essential roles in apoptosis , necrosis, and inflammation....
s that cleave proteins only at an amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
following a aspartic acid
Aspartic acid
Aspartic acid is an α-amino acid with the chemical formula HOOCCHCH2COOH. The carboxylate anion, salt, or ester of aspartic acid is known as aspartate. The L-isomer of aspartate is one of the 20 proteinogenic amino acids, i.e., the building blocks of proteins...
residue. Within this family, caspase 2 is part of the Ich-1 subfamily. It is one of the most conserved caspases in different species
Species
In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are...
of animal. Caspase 2 has a similar amino acid sequence to initiator caspases, including caspase 1
Caspase 1
Caspase 1 is an enzyme that proteolytically cleaves other proteins, such as the precursor forms of the inflammatory cytokines interleukin 1-β and interleukin 18, into active mature peptides...
, caspase 4
Caspase 4
Caspase 4 is an enzyme that proteolytically cleaves other proteins at an aspartic acid residue, and belongs to a family of cysteine proteases called caspases...
, caspase 5
Caspase 5
Caspase 5 is an enzyme that proteolytically cleaves other proteins at an aspartic acid residue, and belongs to a family of cysteine proteases called caspases...
, and caspase 9. It is produced as a zymogen
Zymogen
A zymogen is an inactive enzyme precursor. A zymogen requires a biochemical change for it to become an active enzyme. The biochemical change usually occurs in a lysosome where a specific part of the precursor enzyme is cleaved in order to activate it...
, which contains a long pro-domain that is similar to that of caspase 9 and contains a protein interaction domain known as a CARD domain
CARD domain
Caspase recruitment domains, or Caspase activation and recruitment domains , are interaction motifs found in a wide array of proteins, typically those involved in processes relating to inflammation and apoptosis. These domains mediate the formation of larger protein complexes via direct...
. Pro-caspase-2 contains two subunits, p19 and p12.
It has been shown to associate with several proteins involved in apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
using its CARD domain, including RIP-associated Ich-1/Ced-3-homologue protein with a death domain (RAIDD), apoptosis repressor with caspase recruitment domain (ARC), and death effector filament-forming Ced-4-like apoptosis protein (DEFCAP). Together with RAIDD and p53-induced protein with a death domain ([PIDD])(LRDD
LRDD
Leucine-rich repeats and death domain containing, also known as LRDD or p53-induced protein with a death domain , is a protein which in humans is encoded by the LRDD gene.- Function :...
), caspase 2 has been shown to form the so called PIDDosome, which may serve as an activation platform for the protease, although it may also be activated in the absence of PIDD. In addition, caspase 2 may form a complex with the catalytic subunit of DNA-PK (DNA-PKcs) and PIDD (LRDD
LRDD
Leucine-rich repeats and death domain containing, also known as LRDD or p53-induced protein with a death domain , is a protein which in humans is encoded by the LRDD gene.- Function :...
), which is involved in DNA repair after DNA damage. Overall, caspase 2 appears to be a very versatile caspase with multiple functions beyond cell death induction.
Interactions
Caspase 2 has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with CRADD
CRADD
Death domain-containing protein CRADD is a protein that in humans is encoded by the CRADD gene.-Interactions:CRADD has been shown to interact with RIPK1 and Caspase 2.-Further reading:...
, Caspase 8
Caspase 8
Caspase 8 is a caspase protein, encoded by the CASP8 gene. It most likely acts upon caspase 3.CASP8 orthologs have been identified in numerous mammals for which complete genome data are available...
and BH3 interacting domain death agonist
BH3 interacting domain death agonist
The BH3 interacting-domain death agonist, or BID, gene is a pro-apoptotic member of the Bcl-2 protein family. Bcl-2 family members share one or more of the four characteristic domains of homology entitled the Bcl-2 homology domains , and can form hetero- or homodimers...
.
External links
- The MEROPSMeropsMerops may refer to:* Merops , a genus of bee-eaters.* MEROPS, an on-line database for peptidases.It may also refer to several figures from Greek mythology:* King of Ethiopia, husband of Clymene, who lay with Helios and bore Phaethon...
online database for peptidases and their inhibitors: C14.006